Crosstalk between MiRNAs/lncRNAs and PI3K/AKT signaling pathway in diabetes mellitus: Mechanistic and therapeutic perspectives.

Diabetes as a fastest growing diseases worldwide is characterized by elevated blood glucose levels. There's an enormous financial burden associated with this endocrine disorder, with unequal access to health care between developed and developing countries. PI3Ks (phosphoinositide 3-kinases) have been demonstrated to be crucial for glucose homeostasis, and malfunctioning of these molecules can contribute to an increase in glucose serum levels, the main pathophysiological feature of diabetes. Additionally, recent evidence suggests that miRNAs and lncRNAs are reciprocally interacting with this signaling pathway. It is therefore evident that abnormal regulation of miRNAs/lncRNAs in the lncRNAs/miRNAs/PI3K/AKT axis is related to clinicopathological characteristics and plays a crucial role in the regulation of biological processes. It has therefore been attempted in this review to describe the interaction between PI3K/AKT signaling pathway and various miRNAs/lncRNAs and their importance in DM biology. We also presented the clinical applications of PI3K/AKT-related ncRNAs/herbal medicine in patients with DM.

Comparison of modeling, optimization, and prediction of important parameters in the adsorption of cefixime onto sol-gel derived carbon aerogel and modified with nickel using ANN, RSM, GA, and SOLVER methods.

Today, the main goal of many researchers is the use of high-performance, economically and industrially justified materials, as well as recyclable materials in removing organic and dangerous pollutants. For this purpose, sol-gel derived carbon aerogel modified with nickel (SGCAN) was used to remove Cefixime from aqueous solutions. The influence of important parameters in the cefixime adsorption onto SGCAN was modeled and optimized using artificial neural network (ANN), response surface methodology (RSM), genetic algorithm (GA), and SOLVER methods. R software was applied for this purpose. The design range of the runs for a time was in the range of 5 min-70 min, concentration in the range of 5 mg L-1 to 40 mg L-1, amount of adsorbent in the range of 0.05 g L-1 to 0.15 g L-1, and pH in the range of 2.0-11. The results showed that the ANN model due to lower Mean Squared Error (MSE), Sum of Squared Errors (SSE), and Root Mean Squared Error (RMSE) values and also higher R2 is a superior model than RSM. Also, due to the superiority of ANN over the RSM model, the optimum results were calculated based on GA. Based on GA, the highest Cefixime adsorption onto SGCAN was obtained in pH, 5.98; reaction time, 58.15 min; initial Cefixime concentration, 15.26 mg L-1; and adsorbent dosage, 0.11 g L-1. The maximum adsorption capacity of Cefixime onto SGCAN was determined to be 52 mg g-1. It was found the pseudo-second-order model has a better fit with the presented data.

From molecular pathogenesis to therapy: Unraveling non-coding RNAs/DNMT3A axis in human cancers.

Cancer is a comprehensive classification encompassing more than 100 forms of malignancies that manifest in diverse tissues within the human body. Recent studies have provided evidence that aberrant epigenetic modifications are pivotal indicators of cancer. Epigenetics encapsulates DNA methyltransferases as a crucial class of modifiers. DNMTs, including DNMT3A, assume central roles in DNA methylation processes that orchestrate normal biological functions, such as gene transcription, predominantly in mammals. Typically, deviations in DNMT3A function engender distortions in factors that drive tumor growth and progression, thereby exacerbating the malignant phenotype of tumors. Consequently, such abnormalities pose significant challenges in cancer therapy because they impede treatment efficacy. Non-coding RNAs (ncRNAs) represent a group of RNA molecules that cannot encode functional proteins. Recent investigation attests to the crucial significance of regulatory ncRNAs in epigenetic regulation. Notably, recent reports have illuminated the complex interplay between ncRNA expression and epigenetic regulatory machinery, including DNMT3A, particularly in cancer. Recent findings have demonstrated that miRNAs, namely miR-770-5p, miR-101, and miR-145 exhibit the capability to target DNMT3A directly, and their aberration is implicated in diverse cellular abnormalities that predispose to cancer development. This review aims to articulate the interplay between DNMT3A and the ncRNAs, focusing on its impact on the development and progression of cancer, cancer therapy resistance, cancer stem cells, and prognosis. Importantly, the emergence of such reports that suggest a connection between DNMT3A and ncRNAs in several cancers indicates that this connecting axis offers a valuable target with significant therapeutic potential that might be exploited for cancer management.

A review of the advances, insights, and prospects of gene therapy for Alzheimer's disease: A novel target for therapeutic medicine.

Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid ß (Aß) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges.

Developing nanosize carrier systems for Amphotericin-B: A review on the biomedical application of nanoparticles for the treatment of leishmaniasis and fungal infections.

New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of nano-based technology and nanomaterials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo-polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, nanocapsules, and nanocochleate for Am-B has many advantages to reducing several related issues. The unique properties of nanostructured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new nanocomposite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests.

Tumor-educated platelets.

Beyond traditional roles in homeostasis and coagulation, growing evidence suggests that platelets also reflect malignant transformation in cancer. Platelets are present in the tumor microenvironment where they interact with cancer cells. This interaction results in direct and indirect "education" as evident by platelet alterations in adhesion molecules, glycoproteins, nucleic acids, proteins and various receptors. Subsequently, these tumor-educated platelets (TEPs) circulate throughout the body and play pivotal roles in promotion of tumor growth and dissemination. Accordingly, platelet status can be considered a unique blood-based biomarker that can potentially predict prognosis and therapeutic success. Recently, liquid biopsies including TEPs have received much attention as safe, minimally invasive and sensitive alternatives for patient management. Herein, we provide an overview of TEPs and explore their benefits and limitations in cancer.

microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance.

MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with a short length of 19-22 nucleotides. miRNAs are posttranscriptional regulators of gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is a well-studied miRNA, for which most studies report its downregulation in cancer cells and tissues and experiments support its role as a tumor suppressor inhibiting malignant biological behaviors of cancer cells in vitro and in vivo. To exert its functions, miR-184 affects some signaling pathways involved in tumorigenesis like Wnt and ß-catenin, and AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such as Bcl-2. Interestingly, clinical investigations have shown miR-184 with good performance as a prognostic/diagnostic biomarker for various cancers. Additionally, exogenous miR-184 in cell and xenograft animal studies suggest it as a therapeutic anticancer target. In this review, we outline the studies that evaluated the roles of miR-184 in tumorigenesis as well as its clinical significance.

Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

Non-coding RNAs: A new frontier in benzene-mediated toxicity.

One of the most frequent environmental contaminants, benzene is still widely used as an industrial solvent around the world, especially in developing nations, posing a serious occupational risk. While the processes behind the toxicity of benzene grounds are not fully understood, it is generally accepted that its metabolism, which involves one or more reactive metabolites, is crucial to its toxicity. In order to evaluate the many ways that benzene could influence gene regulation and thus have an impact on human health, new methodologies have been created. The pathophysiology of the disorder may result from epigenetic reprogramming caused by exposure to benzene, including changes in non-coding RNA (ncRNA) markers, according to recent studies. We are interested in the identification of hazardous regulatory ncRNAs, the identification of these ncRNAs' targets, and the comprehension of the significance of these interactions in the mechanisms behind benzene toxicity. Hence, the focus of recent research is on long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), and some of the more pertinent articles are also discussed.

Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance.

Cancer is a complex disease with many contributing factors, and researchers have gained extensive knowledge that has helped them understand the diverse and varied nature of cancer. The altered patterns of DNA methylation found in numerous types of cancer imply that they may play a part in the disease's progression. The human cancer condition involves dysregulation of the DNA methyltransferase 3 beta (DNMT3B) gene, a prominent de novo DNA methyltransferase, and its abnormal behavior serves as an indicator for tumor prognosis and staging. The expression of non-coding RNAs (ncRNAs), which include microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), is critical in controlling targeted gene expression and protein translation and their dysregulation correlates with the onset of tumors. NcRNAs dysregulation of is a critical factor that influences the modulation of several cellular characteristics in cancerous cells. These characteristics include but are not limited to, drug responsiveness, angiogenesis, metastasis, apoptosis, proliferation, and properties of tumor stem cell. The reciprocal regulation of ncRNAs and DNMT3B can act in synergy to influence the destiny of tumor cells. Thus, a critical avenue for advancing cancer prevention and treatment is an inquiry into the interplay between DNMT3B and ncRNAs. In this review, we present a comprehensive overview of the ncRNAs/DNMT3B axis in cancer pathogenesis. This brings about valuable insights into the intricate mechanisms of tumorigenesis and provides a foundation for developing effective therapeutic interventions.

The role of microRNA-185 in the pathogenesis of human diseases: A focus on cancer.

MicroRNAs (miRNAs) are a widely-studied class of non-coding RNAs characterized by their short length (18-25 nucleotides). The precise functions of miRNAs are not well-elucidated; however, an increasing number of studies suggest their involvement in various physiologic processes and deregulation in pathologic conditions. miRNA-185 (miR-185) is among the mostly-studied miRNAs in human diseases, which is found to play putative roles in conditions like metabolic disorders, asthma, frailty, schizophrenia, and hepatitis. Notably, many cancer studies report the downregulation of miR-185 in cell lines, tumor tissues, and plasma specimens of patients, while it demonstrates a suppressing role on the malignant properties of cancer cells in vitro and in vivo. Accordingly, miR-185 can be considered a tumor suppressor miRNA in human malignancies, while a few studies also report inconsistent findings. Being suggested as a prognostic/diagnostic biomarker, mi-185 is also found to offer clinical potentials, particularly for early diagnosis and prediction of the prognosis of cancer patients. In this review, we have outlined the studies that have evaluated the functions and clinical significance of miR-185 in different human diseases with a particular focus on cancer.

microRNA-382 as a tumor suppressor? Roles in tumorigenesis and clinical significance.

MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.

An interplay between non-coding RNAs and gut microbiota in human health.

Humans have a complicated symbiotic relationship with their gut microbiome, which is postulated to impact host health and disease broadly. Epigenetic alterations allow host cells to regulate gene expression without altering the DNA sequence. The gut microbiome, offering environmental hints, can influence responses to stimuli by host cells with modifications on their epigenome and gene expression. Recent increasing data suggest that regulatory non-coding RNAs (miRNAs, circular RNAs, and long lncRNA) may affect host-microbe interactions. These RNAs have been suggested as potential host response biomarkers in microbiome-associated disorders, including diabetes and cancer. This article reviews the current understanding of the interplay between gut microbiota and non-coding RNA, including lncRNA, miRNA, and circular RNA. This can lead to a profound understanding of human disease and influence therapy. Furthermore, microbiome engineering as a mainstream strategy for improving human health has been discussed and confirms the hypothesis about a direct cross-talk between microbiome composition and non-coding RNA.

Understanding the lncRNA/miRNA-NFκB regulatory network in diabetes mellitus: From function to clinical translation.

Diabetes mellitus (DM) and its significant ramifications make out one of the primary reasons behind morbidity worldwide. Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs, are involved in regulating manifold biological processes, including diabetes initiation and progression. One of the established pathways attributed to DM development is NF-κB signaling. Neurons, ß cells, adipocytes, and hepatocytes are among the metabolic tissues where NF-κB is known to produce a range of inflammatory chemokines and cytokines. The direct or indirect role of ncRNAs such as lncRNAs and miRNAs on the NF-κB signaling pathway and DM development has been supported by many studies. As a result, effective diabetes treatment and preventive methods will benefit from a comprehensive examination of the interplay between NF-κB and ncRNAs. Herein, we provide a concise overview of the role of NF-κB-mediated signaling pathways in diabetes mellitus and its consequences. The reciprocal regulation of ncRNAs and the NF-κB signaling pathway in diabetes is then discussed, shedding light on the pathogenesis of the illness and its possible therapeutic interventions.

The impact of particulate matters on apoptosis in various organs: Mechanistic and therapeutic perspectives.

Ecological air contamination is the non-homogenous suspension of insoluble particles into gas or/and liquid fluids known as particulate matter (PM). It has been discovered that exposure to PM can cause serious cellular defects, followed by tissue damage known as cellular stress. Apoptosis is a homeostatic and regulated phenomenon associated with distinguished physiological actions inclusive of organ and tissue generation, aging, and development. Moreover, it has been proposed that the deregulation of apoptotic performs an active role in the occurrence of many disorders, such as autoimmune disease, neurodegenerative, and malignant, in the human population. Recent studies have shown that PMs mainly modulate multiple signaling pathways involved in apoptosis, including MAPK, PI3K/Akt, JAK/STAT, NFκB, Endoplasmic Stress, and ATM/P53, leading to apoptosis dysregulation and apoptosis-related pathological conditions. Here, the recently published data concerning the effect of PM on the apoptosis of various organs, with a particular focus on the importance of apoptosis as a component in PM-induced toxicity and human disease development, is carefully discussed. Moreover, the review also highlighted the various therapeutic approaches, including small molecules, miRNA replacement therapy, vitamins, and PDRN, for treating diseases caused by PM toxicity. Notably, researchers have considered medicinal herbs a potential treatment for PM-induced toxicity due to their fewer side effects. So, in the final section, we analyzed the performance of some natural products for inhibition and intervention of apoptosis arising from PM-induced toxicity.

MicroRNA-122 in human cancers: from mechanistic to clinical perspectives.

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate the expression of target genes post-transcriptionally and interact with mRNA-coding genes. MiRNAs play vital roles in many biological functions, and abnormal miRNA expression has been linked to various illnesses, including cancer. Among the miRNAs, miR-122, miR-206, miR-21, miR-210, miR-223, and miR-424 have been extensively studied in various cancers. Although research in miRNAs has grown considerably over the last decade, much is yet to be discovered, especially regarding their role in cancer therapies. Several kinds of cancer have been linked to dysregulation and abnormal expression of miR-122, indicating that miR-122 may serve as a diagnostic and/or prognostic biomarker for human cancer. Consequently, in this review literature, miR-122 has been analyzed in numerous cancer types to sort out the function of cancer cells miR-122 and enhance patient response to standard therapy.

Non-coding RNAs: An emerging player in particulate matter 2.5-mediated toxicity.

Exposure to air pollution has been connected to around seven million early deaths annually and also contributing to higher than 3 % of disability-adjusted lost life years. Particulate matters (PM) are among the key pollutants that directly discharged or formed due to atmospheric chemical interactions. Among these matters, due of its large surface area, PM2.5 may absorb a different harmful and toxic substances. One of the outcomes of such environmental disturbance is oxidative stress which affects cellular processes including apoptosis, inflammation, and epithelial mesenchymal transition. Non-coding RNAs (ncRNA) such as, miRNAs, lncRNAs, and circRNAs are classified as non-protein coding RNA's. Over the past few years these small molecules have been gaining so much attention since they participate in variety of physiological and pathological processes and their expression change during disease periods. Regarding epigenetic properties, ncRNAs play an important function in organism's response to environmental stimulus. In this manner, it was revealed that exposure to PM2.5 may cause epigenetic reprogramming, such as, ncRNAs signature's alteration, which can be effective concerning pathophysiology state. In this review, we describe PM2.5 impact on ncRNAs and excavate its roles in toxicity caused by PM2.5.

Recent insights into the roles of circular RNAs in human brain development and neurologic diseases.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs. They are single-stranded RNA transcripts characterized with a closed loop structure making them resistant to degrading enzymes. Recently, circRNAs have been suggested with regulatory roles in gene expression involved in controlling various biological processes. Notably, they have demonstrated abundance, dynamic expression, back-splicing events, and spatiotemporally regulation in the human brain. Accordingly, they are expected to be involved in brain functions and related diseases. Studies in animals and human brain have revealed differential expression of circRNAs in brain compartments. Interestingly, contributing roles of circRNAs in the regulation of central nervous system (CNS) development have been demonstrated in a number of studies. It has been proposed that circRNAs play role in substantial neurological functions like neurotransmitter-associated tasks, neural cells maturation, and functions of synapses. Furthermore, 3 main pathways have been identified in association with circRNAs's host genes including axon guidance, Wnt signaling, and transforming growth factor beta (TGF-ß) signaling pathways, which are known to be involved in substantial functions like migration and differentiation of neurons and specification of axons, and thus play role in brain development. In this review, we have an overview to the biogenesis, biological functions of circRNAs, and particularly their roles in human brain development and the pathogenesis of neurodegenerative diseases including Alzheimer's diseases, multiple sclerosis, Parkinson's disease and brain tumors.

MicroRNA-206 in human cancer: Mechanistic and clinical perspectives.

MicroRNAs (miRNAs), small non-coding RNAs approximately 20-25 nt in length, play important roles via directly binding to the corresponding 3' UTR of target mRNAs. Recent research has shown that miRNAs cover a wide range of diseases, including several types of cancer. It is interesting to note that miR-206 operates as a tumor suppressor and is downregulated in abundant cancer types, such as breast cancer, lung cancer, colorectal cancer, and so forth. Interestingly, a growing number of studies have also reported that miR-206 could function as an oncogene and promote tumor cell proliferation. Thereby, miR-206 may act as either oncogenes or tumor suppressors under certain conditions. In addition, it was widely acknowledged that restoring tumor-suppressor miR-206 has emerged as an unconventional cancer therapy strategy. Therefore, miR-206 might be a newfangled procedure for achieving a more significant treatment outcome for cancer patients. This review summarizes the role of miR-206 in several cancer types and the contributions made between miR-206 and the diagnosis, treatment, and drug resistance of solid tumors.

MiR-211 plays a dual role in cancer development: From tumor suppressor to tumor enhancer.

Cancer is a general term for more than 100 unique malignancies in different organs of the body. Each cancer type and subtype has its own unique genetic, epigenetic, and cellular factors accountable for malignant progression and metastasis. Small non-coding RNAs called miRNAs target mRNAs and play a vital part in the pathogenesis of human diseases, specifically cancer. Recent investigations provided knowledge of the deregulation of miR-211 in various cancer types and disclosed that miR-211 has an oncogenic or tumor-suppressive impact on tumourigenesis and cancer development. Moreover, recent discoveries which clarify the essential functions of miR-211 might provide proof for its prognosis, diagnostic and therapeutic impact on cancer. Thereby, this review will discuss recent findings regarding miR-211 expression level, target genes, and mechanisms in different cancers. In addition, the most recent results that propose miR-211 usefulness as a noninvasive biomarker and therapeutic factor for the diagnosis and treatment of cancer will be explained.